Atara's Ebvallo and pipeline candidate put on clinical hold in US after partner's failed plant inspection

After receiving a complete response letter last week, the other shoe has dropped for Atara Biotherapeutics and its pipeline of T-cell immunotherapies.

Atara on Tuesday announced that the FDA has placed a clinical hold on the company’s investigational new drug applications for the Europe-approved Ebvallo in Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+PTLD) and the allogeneic CD19-targeted CAR-T candidate ATA3219 for non-Hodgkin lymphoma and systemic lupus erythematosus.

In turn, screening and enrollment of new patients for both drugs’ development programs have been put on hold. However, certain patients already enrolled in Atara’s studies may continue to receive treatment in line with ongoing study protocols, the company noted in a release.

Atara linked the clinical hold to a lackluster FDA inspection of a third-party manufacturing facility, citing the CRL for Ebvallo it revealed last week.

While drug product for ATA3219 is manufactured at a separate facility than the one implicated in the inspection, the starting materials used in the med’s production are “affected by compliance issues at the same third-party facility referenced in the CRL,” Atara explained.

The company was quick to point out that another of its third-party manufacturing plants, which is operated by Fujifilm Diosynth Biotechnologies in Thousand Oaks, California, is unconnected to the current hold and CRL. The Fujifilm facility “remains a critical component” of Atara’s manufacturing strategy, the company noted.

Atara has been working “as expeditiously as possible" with the FDA on the steps needed to lift the regulator’s clinical hold, CEO Cokey Nguyen, Ph.D., said in a statement. 

News of the clinical hold follows Atara’s announcement that it received a CRL tied to its Ebvallo application. At the time, the company said the filing slap-down was “solely related to inspection findings” at the unnamed third-party manufacturer, stressing that the FDA didn’t raise any concerns around the drug’s efficacy or safety data.

“Once the third-party manufacturer GMP compliance issues have been adequately addressed, we will file for a resubmission, which we would expect to be potentially approved within six months of resubmission," Nguyen said in a press release last week.

Atara is working together with Pierre Fabre Laboratories in a bid to secure approval for Ebvallo in EBV+PTLD for U.S. patients who’ve received at least one prior therapy for their disease.

The drug, which also goes by the name tabelecleucel, was approved in Europe back in December 2022, becoming the first allogeneic—or off-the-shelf—T-cell therapy to score a green light anywhere.

Unlike the more common crop of autologous cell therapies, which leverage a patient’s own cells for treatment, allogeneic therapies utilized modified cells from healthy donors. The approach, which has been much touted but largely unrealized as of yet, is expected to help avoid some of the common manufacturing and logistics hurdles that have stymied prior cell therapy launches.

As for Pierre Fabre, the company first linked up with Atara as part of a 2021 Ebvallo commercialization agreement spanning Europe, the Middle East, Africa and certain other markets. The companies reunited in 2023 under a separate deal worth up to $640 million that put Pierre Fabre in charge of manufacturing, clinical and regulatory activities for Ebvallo in the U.S.